The studies proposed here were designed as a coordinated effort to define the behavioral and neurophysiological effects of acute and chronic cadmium administration, the sensitivity of the rat to cadmium at major developmental stages, and the potential interrelations between essential trace metal balance and cadmium toxicity. In the studies of chronic Cd exposure we will (a) assess the effects on selected behavioral and neurophysiological parameters such as spontaneous locomotor activity, motor coordination, aggressiveness, learning, peripheral nerve conduction velocity, visual evoked response and skeletal muscle contractile force; (b) determine the relative effects of Cd exposure during the pre-gestational, gestational, neonatal, and adult periods, and (c) determine the concentration of Cd, Fe, Zn, and Cu in selected tissues to ascertain whether changes in trace metal balance may be associated with the occurrence of signs of neurotoxicity. In the acute exposures and in vitro work our objectives are to (a) elucidate the mechanism of action of Cd as a synaptic blocking agent and (b) determine the effects of localized brain injections of Cd and whether particular brain loci are more sensitive than others. Our overall objective in these studies is to provide a comprehensive assessment of the neurotoxic effects of cadmium, including the possibly crucial role that essential trace metals may have in determining toxicity.